Abstract
We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. These animals showed no fever and no central prostaglandin (PG) E2 synthesis after peripheral injection of bacterial-wall lipopolysaccharide, but their pyretic capacity in response to centrally administered PGE2 was intact. Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Temperature / drug effects
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Brain / drug effects
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Brain / immunology
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Dinoprostone / cerebrospinal fluid
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Dinoprostone / pharmacology
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Disease Models, Animal
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Fever / chemically induced
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Fever / immunology*
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Fever / physiopathology
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Gene Expression Regulation, Enzymologic
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Intramolecular Oxidoreductases / deficiency
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Intramolecular Oxidoreductases / genetics
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Intramolecular Oxidoreductases / metabolism
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Intramolecular Oxidoreductases / physiology*
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Knockout
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Microsomes / enzymology*
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Prostaglandin-E Synthases
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RNA, Messenger / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction / methods
Substances
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Lipopolysaccharides
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RNA, Messenger
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Intramolecular Oxidoreductases
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Prostaglandin-E Synthases
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Ptges protein, mouse
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Dinoprostone